Use of antimicrobial proteins and peptides for the treatment of otitis media and paranasal sinusitis

a technology of paranasal sinusitis and antimicrobial proteins, which is applied in the direction of antibacterial agents, peptide/protein ingredients, transferrins, etc., can solve the problems of reducing the number of effective antibiotics, affecting the treatment effect, and posing a major public health threat, so as to achieve reasonable prices

Inactive Publication Date: 2006-06-13
HOUSE EAR INSTITUTE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Otitis media and sinusitis are two very common infections which are difficult to treat for a number of reasons, including antibiotic resistance.
OM results in 31 million annual visits to physicians' offices and is estimated to have a yearly cost exceeding $5 billion.
This has resulted in a reduction of the number of effective antibiotics for this disease and begun to pose a major public health threat.
Thus, the use of antibiotics is becoming more complicated as resistance increases, necessitating the testing of microbes before treatment, which can sometimes fatally delay the necessary treatment.
In addition, wide antibiotic use is further contributing to the problem of resistance.
The need to identify new antibiotics is causing the price of these substances to be so high as to be prohibitive in some cases.

Method used

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  • Use of antimicrobial proteins and peptides for the treatment of otitis media and paranasal sinusitis
  • Use of antimicrobial proteins and peptides for the treatment of otitis media and paranasal sinusitis
  • Use of antimicrobial proteins and peptides for the treatment of otitis media and paranasal sinusitis

Examples

Experimental program
Comparison scheme
Effect test

example 1

Expression of Innate Immune Molecules: Lysozyme, Lactoferrin, and Human Beta Defensins in the Middle Ear and the Middle Ear Mucosa Normally and in Response to Pathogens

[0063]As shown in FIG. 1, a gel overlay assay was performed to show that experimentally induced effusion in rats contained molecules electrophoretically consistent with the molecules of innate immunity and which had anti-microbial activity. Rats were inoculated with 1.0 mg of S. typhimurium endotoxin in 100 μl of sterile saline. Animals were sacrificed after 48 hours and the effusion was collected. The microbicidal activity of the samples was then evaluated using the gel over-lay assay. The radial assay-method of Lehrer and coworkers was used, with minor modifications (Lehrer et al., 1991). The subcultured bacteria (4×106 CFU / 10 ml underlay gel) were mixed with melted underlay gel at 42° C. (0.1× culture broth—BHI for NTHi and Moraxella and THB for S. pneumoniae-10 mM sodium phosphate, 0.8% low electroendosmosis (EEO)...

example 2

The Effect of Lysozyme, Lactoferrin and Human Beta-Defensins on OM Pathogens

[0068]The radial assay method of Lehrer and coworkers was used, with minor modifications (Lehrer et al., 1991). The subcultured bacteria (4×106 CFU / 10 ml underlay gel) were mixed with melted underlay gel at 42° C. (0.1× culture broth—BHI for NTHi and Moraxella and THB for S. pneumoniae-10 mM sodium phosphate, 0.8% low electroendosmosis (EEO)-type agarose) and poured into 8 cm×8 cm square petri plates. The gel was allowed to solidify in the petri plates and wells were punched out with a calibrated 200 μl micropipette tip, cut off at the 50 μl mark (approximately 3 mm). The antimicrobial peptides and proteins were dissolved in 0.01% acetic acid and 4 μl was added to each well. The plates were then incubated for 3 hours at 37° C. in the 5% CO2 incubator. They were next overlaid with the overlay gel (0.5× culture broth, 10 mM sodium phosphate, 0.8% low EEO-type agarose) and covered. The plates were then allowed ...

example 3

Dose Response Analysis

[0072]A dose response analysis is performed for each molecule in order to determine the concentration range where the best effect is observable as well as a synergistic effect of different combinations. Thus, various concentrations of lactoferrin with various concentrations of defensins are used as in Example 1 and the concentrations at which maximum effectiveness of the combination occurs are used in further treatments.

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Abstract

Disclosed herein is a composition and a method for the treatment of otitis media and paranasal sinusitis using human defensins, lysozyme and / or lactoferrin as a new class of non-antibiotic antimicrobials. From studies of otitis media and paranasal sinusitis, it was observed that certain innate immune modulators were important in the bodies response to the infection. Therefore, these innate immune modulators, lysozyme, lactoferrin, and defensins were tested for use as a non-antibiotic treatment for infection, particularly infections such as otitis media and sinusitis.

Description

RELATED APPLICATIONS[0001]This application is a continuation of U.S. patent application Ser. No. 09 / 998,547 filed Nov. 27, 2001, now U.S. Pat. No. 6,716,813, which claims priority of the U.S. Provisional Application 60 / 253,492, filed Nov. 20, 2000, both of which are herein incorporated by reference in their entireties.[0002]This invention was made with U.S. Government support under grant NIH NIDCD R01 DC05025. The U.S. Government has certain rights in the invention.FIELD OF THE INVENTION[0003]The invention relates generally to the use of human beta defensins, lysozyme, and lactoferrin as a new class of non-antibiotic antimicrobials. More specifically, the invention relates to the use of these antimicrobials for the treatment of otitis media and paranasal sinusitis.BACKGROUND OF THE INVENTION[0004]The rapid worldwide increase in antibiotic resistance among pathogens has given rise to an urgent need to develop new and innovative non-antibiotic approaches to prevent and manage disease....

Claims

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Application Information

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Patent Type & Authority Patents(United States)
IPC IPC(8): A61K38/00A61K38/17A61K38/40A61K38/47
CPCA61K38/1709A61K38/47A61K38/40A61K38/1729A61K2300/00
Inventor LIM, DAVID J.LEE, HAA-YUNGWEBSTER, PAULANDALIBI, ALILI, JIAN-DONGGANZ, TOMAS
Owner HOUSE EAR INSTITUTE
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